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Transcriptomic profiling of the oocyte-cumulus-granulosa cell complex from estrogen receptor ß knockout mice.
Töhönen, Virpi; Antonson, Per; Boggavarapu, Nageswara Rao; Ali, Heba; Motaholi, Leticia Apolinario; Gustafsson, Jan-Åke; Varshney, Mukesh; Rodriguez-Wallberg, Kenny A; Katayama, Shintaro; Nalvarte, Ivan; Inzunza, Jose.
Afiliación
  • Töhönen V; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Antonson P; Department of Medicine Huddinge, Karolinska Institutet, Huddinge, Sweden.
  • Boggavarapu NR; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
  • Ali H; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Visionsgatan, Solna, Sweden; Department of Biochemistry, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt.
  • Motaholi LA; Department of Medicine Huddinge, Karolinska Institutet, Huddinge, Sweden.
  • Gustafsson JÅ; Department of Medicine Huddinge, Karolinska Institutet, Huddinge, Sweden; Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, Texas.
  • Varshney M; Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.
  • Rodriguez-Wallberg KA; Department of Oncology-Pathology, Laboratory of Translational Fertility Preservation, Karolinska Institutet, Stockholm, Sweden; Division of Gynecology and Reproduction, Department of Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden.
  • Katayama S; Department of Medicine Huddinge, Karolinska Institutet, Huddinge, Sweden; Folkhälsan Research Center, Helsinki, Finland; Stem Cells and Metabolism Research Program, University of Helsinki, Helsinki, Finland.
  • Nalvarte I; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Visionsgatan, Solna, Sweden.
  • Inzunza J; Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden. Electronic address: jose.inzunza@ki.se.
F S Sci ; 2024 Aug 19.
Article en En | MEDLINE | ID: mdl-39168303
ABSTRACT

OBJECTIVE:

To study the role of estrogen receptor ß in follicle development and maturation and the response to gonadotropin stimulation aiming at superovulation.

DESIGN:

Experimental study and transcriptomic analysis.

SETTING:

Karolinka Institutet, medical university. ANIMAL(S) Healthy wild-type (WT) and estrogen receptor ß knockout (Esr2-KO) female mice undergoing superovulation at 4 weeks, 7 weeks, and 6 months of age. INTERVENTION(S) Not applicable. MAIN OUTCOME MEASURE(S) Oocyte yield after superovulation, transcriptomic profiling of cumulus-granulosa cell complexes and oocytes, and immunohistochemical analyses. RESULT(S) Superovulation of estrogen receptor ß (ERß) knockout mice resulted in reduced oocyte yield at 6 months of age compared with WT mice, but younger mice had similar yields. RNA-seq analysis of cumulus cells from superovulated WT and Esr2-KO mice identified genes and pathways associated with among others adhesion, proliferation, Wnt-signaling, and placed ERß in bipotential granulosa cell cluster. Loss of ERß increased expression of the other estrogen receptors Esr1 and Gper1. CONCLUSION(S) Our results show that ERß has an important role in regulating ovulation in response to exogenous gonadotropins in 6-month-old mice, but not in younger mice. Our transcriptomic and immunohistochemical observations suggest a dysregulation of the granulosa cell communication and lack of tight coordination between granulosa cell replication and antrum expansion. A significant upregulation of other estrogen receptors may support a compensatory mechanism sustaining fertility during younger age in Esr2-KO mice.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: F S Sci Año: 2024 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: F S Sci Año: 2024 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos